There are more than two million people infected with hepatitis C virus (HCV) in Japan, among which about 36,000 people develop hepatocarcinoma every year where most of the cancer patients result in death. Currently, interferon (IFN) is used as the only effective anti-HCV drug, which has limited effect and serious side-effects. Thus, there is a demand for development of a safer and more effective drug. Furthermore, since aging of the infected people increases the risk of developing cancer, there is a need for urgent remedy.
At the current moment, drugs such as nucleic acid analogs, protease inhibitors and the like that suppress viral replication of HCV have been developed and used for treatment. In treatment using these drugs, however, a drug-resistant virus is likely to emerge, and complete elimination of the virus is difficult in view of the mechanisms of this action of the virus, thus a lifelong medication is necessary. In such circumstances, there has been a strong desire for establishment of a curative therapy that allows withdrawal and relief from lifelong medication.
The present inventors have established various experimental model systems, namely, research sources in association with HCV studies by preparing an infectious cDNA clone of HCV and establishing infected animals such as HCV-infectious transgenic mice and human liver chimeric mice and the like (e.g., see Non-patent Document 1). The major features of HCV infection include establishment of persistent infection at a high rate and progress to chronic hepatitis. The present inventors have gone through keen analyses and examinations over the years using the above-mentioned experimental model systems and the like by looking at this mechanism of action in terms of acquisition of immunological tolerance and breakdown thereof (e.g., see Non-patent Document 2).
Numerous attempts to develop a vaccine for preventing HCV infection have been made heretofore but so far none of them provided complete prevention of infection (e.g., see Non-patent Documents 3, 4, 5 and 6).    Non-patent Document 1: Wakita T., et al., J. Biol. Chem., 1998, vol. 273, p9001-9006    Non-patent Document 2: Inoue K., et al., Hepatology, 2007, vol. 45, p921-928    Non-patent Document 3: Choo Q L., et al., Pros. Natl. Acad. Sci. 1994, vol. 91, 1294-1298    Non-patent Document 4: Puig M., et. al., Vaccine 2004, vol. 22, 991-1000    Non-patent Document 5: Abraham J D., Vaccine 2004, vol. 22, 3917-3928    Non-patent Document 6: Elmowalid G A., et. al., Pros. Natl. Acad. Sci. 2007, vol. 104, 8427-8432